Afinitor

everolimus

About

This is a summary of the European public assessment report (EPAR) for Afinitor. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Afinitor.

breast cancer that is advanced (has started to spread) in women who have been through their menopause. Afinitor is used in breast cancer that is ‘hormone receptor-positive’ (when the cancer cells have oestrogen receptors on their surface) and ‘HER2/neu negative’ (when the cancer cells do not contain high levels of the HER2/neu [human epidermal growth factor receptor-2] protein). It is used together with a medicine called exemestane after other treatments called ‘non-steroidal aromatase inhibitors’ have failed;

pancreatic neuroendocrine tumours (tumours of the hormone-producing cells in the pancreas) when the cancer cells are well- or moderately differentiated (which means that they have a similar appearance to normal pancreas cells) and the cancer is getting worse. It is used when the cancer is metastatic (has spread to other parts of the body) or when it cannot be surgically removed;

neuroendocrine tumours originating in the lungs or gut, when the cancer cells are well-differentiated and the cancer is metastatic or cannot be removed by surgery.

Treatment with Afinitor should be started and supervised by a doctor who has experience in the use of cancer treatments.

The recommended dose of Afinitor is 10 mg once a day. Treatment should continue for as long as the patient benefits from it or until the patient develops unacceptable side effects. The doctor may reduce the dose or stop treatment for a short period if the patient has severe or intolerable side effects. Doses need to be reduced for patients with liver problems.

The tablets should be swallowed whole at the same time every day and should not be chewed or crushed. They should be taken consistently with or without food.

The active substance in Afinitor, everolimus, is a cancer medicine, which acts by blocking a protein called ‘mammalian target of rapamycin’ (mTOR). In the body, everolimus first attaches to a protein called FKBP-12 that is found inside cells to make a ‘complex’. This complex then blocks mTOR. Since mTOR is involved in the control of cell division and the growth of blood vessels, Afinitor prevents the division of tumour cells and reduces their blood supply. This slows down the growth and spread of the tumours.

The effects of Afinitor were studied in four main studies. The first study involved 724 patients with hormone receptor-positive and HER2/neu-negative advanced breast cancer which had got worse after treatment with letrozole and anastrazole (‘non-steroidal aromatase inhibitors’ cancer medicines). In addition, all patients in this study received exemestane.

The fourth study was done in 302 patients with advanced neuroendocrine tumours of lung or gutorigin. Patients who received Afinitor and best supportive treatments were compared with patients who received placebo (a dummy treatment) and best supportive treatments to relieve disease symptoms.

The main measure of effectiveness in the four studies was how long the patients lived without the disease getting worse.

The most common side effects with Afinitor (which may affect more than 1 in 10 people) are rash, pruritus (itching), nausea, decreased appetite, dysgeusia (taste disturbances), headache, decreased weight, peripheral oedema (swelling, especially of the ankles and feet), cough, anaemia (low red blood cell counts), fatigue (tiredness), diarrhoea, asthenia (weakness), infections, stomatitis (inflammation of the lining of the mouth), hyperglycaemia (high blood glucose levels), hypercholesterolaemia (high blood cholesterol levels), pneumonitis (inflammation of the lungs) and epistaxis (nosebleeds). For the full list of all side effects reported with Afinitor, see the package leaflet.

Afinitor must not be used in people who are hypersensitive (allergic) to other rapamycin derivatives (substances with a similar structure to everolimus) or to any of the other ingredients. For the full list of restrictions, see the package leaflet.

The CHMP decided that Afinitor was shown to slow down disease progression in patients with advanced neuroendocrine tumours of pancreatic origin, advanced renal cell carcinoma and hormone-receptor-positive advanced breast cancer. The CHMP also concluded that the 7 month delay in disease progression for patients with neuroendocrine tumours originating in the lungs or gut was clinically relevant, despite the known side effects of Afinitor. The CHMP concluded that the benefits of Afinitor are greater than its risks and recommended that it be granted marketing authorisation.

The company that makes Afinitor will provide the results of a main study comparing treatment with Afinitor alone, treatment with Afinitor and exemestane in combination, and treatment with capecitabine (another cancer medicine). This study is being done in patients with oestrogen-receptor positive breast cancer that has spread or progressed after previous treatment with letrozole or anastrozole.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Afinitor have also been included in the summary of product characteristics and the package leaflet.

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Hormone-receptor-positive advanced breast cancer

Afinitor is indicated for the treatment of hormone-receptor-positive, HER2/neu-negative advanced breast cancer, in combination with exemestane, in post-menopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor.

Neuroendocrine tumours of pancreatic origin

Afinitor is indicated for the treatment of unresectable or metastatic, well or moderately differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease.

Neuroendocrine tumours of gastrointestinal or lung origin

Afinitor is indicated for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease.

Renal-cell carcinoma

Afinitor is indicated for the treatment of patients with advanced renal-cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy.

Related information

More information on Afinitor

This product is no longer an orphan medicine. It was originally designated an orphan medicine on 5 June 2007. Upon request of the marketing-authorisation holder, Afinitor has now been removed from the Community register of orphan medicinal products.